Clinical outcomes of patients with respiratory azole-resistant Aspergillus fumigatus in Barcelona, Spain

Abstract Objective To determine the prevalence of azole-resistant A. fumigatus (ARAF) respiratory isolates and its clinical relevance. Methods Retrospective, single-center study of adult patients with ≥ 1 respiratory ARAF isolate (resistance to ≥ 1 triazole according to EUCAST) between May 2022 and December 2024. The primary outcome was the rate of ARAF among all A. fumigatus sensu stricto (ss) isolates. The prevalence of aspergillosis and 90-day mortality were assessed as secondary endpoints. Results Among 476 patients with A. fumigatus ss isolates, ARAF was identified in 75 (16%); 66 had available clinical data to be finally included. Compared to colonized individuals (n = 56, 85%), patients with aspergillosis (n = 10, 15%) were more frequently immunosuppressed (8/56 vs 6/10, p < 0.01). Six patients had invasive aspergillosis (IA), 3 of whom received azole-based inadequate empirical treatment. Forty-five (68%) patients had a pan-azole resistant phenotype but only 14 (21%) had prior antifungal exposure. Overall, the 90-day attributable mortality was 6%. Among patients with fungal disease, 90-day attributable mortality reached 40%, increasing to 67% in IA. Conclusions In our setting, the prevalence of ARAF was high and mainly reflected colonization. Invasive disease was uncommon but associated high mortality rates. Active empirical therapy against ARAF should be considered in high-risk patients with invasive aspergillosis until azole-resistance is excluded.